chr8-98123347-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001145860.2(POP1):c.10G>C(p.Ala4Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4T) has been classified as Benign.
Frequency
Consequence
NM_001145860.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POP1 | NM_001145860.2 | c.10G>C | p.Ala4Pro | missense_variant | 2/16 | ENST00000401707.7 | |
POP1 | NM_001145861.2 | c.10G>C | p.Ala4Pro | missense_variant | 2/16 | ||
POP1 | NM_015029.3 | c.10G>C | p.Ala4Pro | missense_variant | 2/16 | ||
POP1 | XM_011516801.3 | c.10G>C | p.Ala4Pro | missense_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POP1 | ENST00000401707.7 | c.10G>C | p.Ala4Pro | missense_variant | 2/16 | 2 | NM_001145860.2 | P1 | |
POP1 | ENST00000349693.3 | c.10G>C | p.Ala4Pro | missense_variant | 2/16 | 1 | P1 | ||
POP1 | ENST00000522319.5 | c.10G>C | p.Ala4Pro | missense_variant | 2/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251424Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135894
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461316Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727008
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 13, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with POP1-related conditions. This variant is present in population databases (rs145484648, ExAC 0.002%). This sequence change replaces alanine with proline at codon 4 of the POP1 protein (p.Ala4Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at